Assessing the Endometrial Environment in Recurrent Pregnancy Loss and Unexplained Infertility

NCT ID: NCT03401918

Last Updated: 2025-04-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-01
• Study Completion Date: 2021-07-01

Brief Summary

The purpose of this study is to determine if patients with recurrent pregnancy loss or unexplained infertility have an altered uterine gene expression or uterine microbiome (micro-organism composition) during the window of embryo implantation. Furthermore we would like to assess for women with an abnormal uterine gene expression whether vaginal progesterone medication improves or alters gene expression and for women with an abnormal microbiome whether antibiotic treatment followed by probiotic treatment normalizes the microbiome.

Detailed Description

Recurrent pregnancy loss and unexplained infertility are emotional and difficult diagnoses. Despite a thorough medical investigation, many cases of recurrent pregnancy loss and infertility remain unexplained. Understanding endometrial factors that may contribute to these diseases may lead to improved treatment options in the future. The purpose of this study is to determine if patients with recurrent pregnancy loss or unexplained infertility have an altered uterine gene expression or uterine microbiome (micro-organism composition) during the window of embryo implantation. Furthermore we would like to assess for women with an abnormal uterine gene expression whether vaginal progesterone medication improves or alters gene expression and for women with an abnormal microbiome whether antibiotic treatment followed by probiotic treatment normalizes the microbiome.

A standard evaluation for infertility includes a uterine cavity evaluation, evaluation for ovarian reserve testing, and for patients with recurrent pregnancy loss parental testing for uterine infection, chromosome analysis, autoimmune and thyroid screening. This standard workup, however, does not include a molecular or microbial assessment of the endometrium. Endometrial factors may contribute to unexplained infertility or recurrent pregnancy loss however the extent of this is unknown.

We are recruiting patients who have recurrent pregnancy loss, unexplained infertility, and healthy control patients who have had a term delivery in order to compare differences between these groups.

Subjects will undergo an endometrial biopsy that will specifically test the receptivity of your endometrium as well as identify the bacterial composition of the uterine environment (microbiome). The endometrial receptivity array and microbiome testing will be performed at no cost. The endometrial receptivity array provides information on the receptivity of a patient's endometrium to the implantation of an embryo. This may yield additional information regarding the etiology of a patient's infertility and/or recurrent pregnancy loss. If this testing is abnormal we may repeat the biopsy after vaginal progesterone supplementation to see if this normalizes the results. If the microbiome is abnormal we may repeat the biopsy after oral antibiotics and vaginal probiotics to see if this normalizes your microbiome results.

Conditions

Recurrent Pregnancy Loss; Unexplained Infertility

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Patients with recurrent pregnancy loss or unexplained infertility

Patients with recurrent pregnancy loss or unexplained infertility will have an assessment of the uterine environment at the time of implantation, followed by testing of uterine endometrial gene expression using the ERA test and the uterine micro biome.

Those who have abnormal results (an abnormal microbiome or an abnormal ERA) will have the option to undergo treatment followed by retesting of the uterine environment. For an abnormal ERA suggesting a pre-receptive result, luteal phase vaginal progesterone supplementation will be offered prior to re-testing of the ERA. For an abnormal microbiome a combination of oral antibiotics and vaginal probiotics will be offered prior to re-testing the uterine microbiome.

Group Type: EXPERIMENTAL

Uterine ERA and microbiome testing

Intervention Type: DIAGNOSTIC_TEST

Uterine fluid and endometrial biopsy collection to test uterine endometrial receptivity array and microbiome.

Oral antibiotics and vaginal probiotics

Intervention Type: DRUG

For subjects with abnormal microbiome results, oral antibiotics and vaginal probiotic treatment will be offered followed by a repeat uterine microbiome biopsy.

Healthy Control Patients

Patients who have had a normal delivery and no history of infertility or recurrent pregnancy loss will have assessment of the uterine environment at the time of implantation.

Group Type: EXPERIMENTAL

Uterine ERA and microbiome testing

Intervention Type: DIAGNOSTIC_TEST

Uterine fluid and endometrial biopsy collection to test uterine endometrial receptivity array and microbiome.

Interventions

Uterine ERA and microbiome testing

Uterine fluid and endometrial biopsy collection to test uterine endometrial receptivity array and microbiome.

Intervention Type: DIAGNOSTIC_TEST

Oral antibiotics and vaginal probiotics

For subjects with abnormal microbiome results, oral antibiotics and vaginal probiotic treatment will be offered followed by a repeat uterine microbiome biopsy.

Intervention Type: DRUG

Eligibility Criteria

Exclusion Criteria

1. Recurrent Pregnancy Loss

Inclusion:

• Age 18-45
• 3 or more SABs including biochemical pregnancies OR 2 or more SABs if one is documented to be euploid

Exclusion:

• irregular menstrual cycles
• Submucosal fibroid >3cm
• Stage 3-4 endometriosis
• BMI >40
• IUD within the last 3 months

2. Unexplained infertility Patients

Inclusion:

• TTC x >= 1 year
• At least one SA with TMS >10 mil within last 2 years
• At least one patent fallopian tube documented by HSG or SHG
• Cycle length 25-35 days

Exclusion:

• Irregular menstrual cycles
• Submucosal fibroid >3cm
• Stage 3-4 endometriosis
• BMI >40
• IUD within the last 3 months
• Less then 2 SABs including biochemical pregnancies

3. Healthy control patients

Inclusion:

• Patients who present for fertility preservation, sex selection, same sex couples needing fertility care, preconception counseling
• 1 or more live births

Exclusion:

• Irregular menstrual cycles
• Submucosal fibroid >3cm
• Stage 3-4 endometriosis
• BMI >40
• IUD within the last 3 months
• Less then 2 SABs including biochemical pregnancies
• No history of RPL or infertility

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Instituto Valenciano de Infertilidad, IVI VALENCIA

OTHER

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Ruth Bunker Lathi

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Reproductive Endocrinology and Infertility Center at Stanford University

Sunnyvale, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

40761

Identifier Type: -

Identifier Source: org_study_id